Effects of selected opioid agonists and antagonists on DMT- and LSD-25-induced disruption of food-rewarded bar pressing behavior in the rat.
Several opioid agonists and antagonists interact with N,N-dimethyltryptamine (DMT) and lysergic acid diethylamide-25 (LSD) in adult male Holtzman rats trained on a positive reinforcement, fixed ratio 4  (FR4) behavioral schedule, i.e., a reward of 0.01 ml sugar-sweetened milk was earned on every fourth bar press. DMT (3.2 and 10.0 mg/kg) and LSD (0.1 mg/kg) given IP with 0.9% NaCl pretreatment, disrupted food-rewarded FR4 bar pressing. Animals were pretreated IP (10--15 min) with predetermined, behaviorally noneffective doses of morphine, methadone, naltrexone, and the (+)- and (-)-enantiomers of naloxone prior to receiving DMT or LSD. Dose-dependent effects were shown with opioid agonist pretreatment. Morphine (0.32--1.0 mg/kg) and methadone (0.32 mg/kg) significantly antagonized the bar pressing disruption induced by DMT and LSD. Larger doses of morphine (3.2 mg/kg) and methadone (1.0--3.2 mg/kg) potentiated only LSD-induced effects, with no effect on DMT-treated groups. The opioid antagonists (-)-naloxone and naltrexone potentiated the disruption of bar pressing induced by DMT and LSD. Failure of (+)-naloxone to potentiate the DMT effects was attributed to a stereo-specific opioid antagonist effect of (-)-naloxone.
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D004347:Drug Interactions; D004357:Drug Synergism; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008297:Male; D008691:Methadone / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D004130:N,N-Dimethyltryptamine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D012054:Reinforcement, Psychology; D014363:Tryptamines / Q000494:pharmacology*
D009294:Narcotics; D014363:Tryptamines; D009270:Naloxone; D009271:Naltrexone; D009020:Morphine; D008238:Lysergic Acid Diethylamide; D008691:Methadone; D004130:N,N-Dimethyltryptamine